Abstract: The era of screening for prostate cancer (PCa) using serum prostate specific antigen (PSA) has led to an increase in the detection of low-grade prostate cancers that pose little risk of either metastatic spread or death. Additionally, these men may be now exposed to morbidities of over treatment with little or no benefit of cancer-specific survival. Active surveillance (AS) has thus evolved as a recommended management strategy for men with low grade disease, providing the benefit of an individualized approach of carefully monitoring disease progression, sufficient to permit timely therapeutic intervention. However, concerns about under- grading, variations in criteria for AS eligibility, patient reported anxiety, depression, doubts about the possible progression of the disease as well as higher decisional conflict regarding selection of AS, men on AS have been reported to ultimately opt for treatment without any major change in tumor characteristics. On the other hand, men on AS are a subgroup, who are highly motivated and eager to make positive lifestyle changes to further reduce their risk of PCa progression- providing an opportunity for chemoprevention. Chemoprevention strategies with 5-alpha-reductase inhibitors significantly reduced the risk of prostate cancer progression. However their use was also associated with increased detection of high- grade disease, severely limiting their clinical adoption. Currently, there is a paucity of research that systematically examines agents for chemoprevention in men on AS. Green tea catechins (GTC) influence several hallmarks of carcinogenesis, including prostate carcinogenesis, with an acceptable safety profile, making them attractive candidates for PCa chemoprevention. Several epidemiological, in vitro, preclinical and early phase trials completed by our team and others have shown that the GTC are potent inhibitors of PCa carcinogenesis through multiple mechanisms, bioavailable in tissue and plasma, reduces several intermediate biomarkers implicated in PCa progression and without toxicities at these doses. Based on the available evidence, we hypothesize that men with biopsy proven adenocarcinoma of the prostate who meet the criteria for AS, who receive GTC at a dose of 800 mg EGCG per day (vs. placebo) for 24 months, will have a significantly decreased rate of clinical progression. We will test this hypothesis using a rigorous experimental design in a phase II, randomized clinical trial to evaluate the safety, effectiveness and potential mechanism by which GTC modulates clinical progression and the related biological biomarkers relevant to PCa progression in men on AS for PCa. Positive results from this study will be critical to inform development a phase III clinical trial and ultimately provide a strategy for secondary chemoprevention in men on AS, for whom, currently, there are no options for reducing risk of progression to PCa.